This project seeks to determine the location and mechanism of neurotransmitter secretion and reception. Rapid freezing and subsequent freeze-fracture of synapses visualizes fleeting structural changes in the cell membrane accompanying discharge of synatic vesicles. This approach has shown that each quantum of transmitter is released by one synaptic vesicle. Structural details which may be specific for different pharmacological types of synapses are being investigated by examining postsynaptic membrane structure. New methods are being tried for marking specific entities, such as receptors, to identify them in freeze-fracture and thin section preparations. This work is significant in that it defines the normal structure of synapses and relates normal variations in structure to different functional states. Thus, it becomes possible to distinguish pathological changes in structure, an issue of great importance in studying the etiology of epilepsy or myasthenia gravis. The current program also includes freeze-fracture of developing synapses, which will aid in understanding of both normal development and developmental failures in the brain and peripheral nervous system. BIBLIOGRAPHIC REFERENCES: Gulley, R.L. and Reese, T.S.: Freeze-fracture studies of synapses on the organ of Corti. J. Comp. Neurol. 171: 517-544, 1977. Dubois-Dalcq, M., Rodriguez, M., Reese, T.S., Gibbs, Jr., C.C. and Gajdusek, D.C.: Search for a specific marker in the neural membranes of scrapie mice (a freeze-fracture study). Lab Invest. 36: 547-563, 1977.